Metallic implantable grafts and method of making same

ABSTRACT

Implantable medical grafts fabricated of metallic or pseudometallic films of biocompatible materials having a plurality of microperforations passing through the film in a pattern that imparts fabric-like qualities to the graft or permits the geometric deformation of the graft. The implantable graft is preferably fabricated by vacuum deposition of metallic and/or pseudometallic materials into either single or multi-layered structures with the plurality of microperforations either being formed during deposition or after deposition by selective removal of sections of the deposited film. The implantable medical grafts are suitable for use as endoluminal or surgical grafts and may be used as vascular grafts, stent-grafts, skin grafts, shunts, bone grafts, surgical patches, non-vascular conduits, valvular leaflets, filters, occlusion membranes, artificial sphincters, tendons and ligaments.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 10/840,205, filed May 6, 2004, which claims priority toprovisional application, U.S. Ser. No. 60/468,425, filed May 7, 2003,and is related to commonly assigned, U.S. application Ser. No.10/135,136 filed Apr. 29, 2002, now U.S. Pat. No. 7,300,457, whichclaims priority from U.S. Ser. No. 60/310,617, filed Aug. 7, 2001, U.S.Ser. No. 09/745,304, filed Dec. 22, 2000, now U.S. Pat. No. 6,820,676,which is a divisional of Ser. No. 09/443,929, filed Nov. 19, 1999, nowU.S. Pat. No. 6,379,383, and U.S. Ser. Nos. 10/289,974 and 10/289,843both filed Nov. 6, 2002, now U.S. Pat. Nos. 7,491,226 and 7,641,680,which are continuation applications of U.S. Ser. No. 09/532,164, filedMar. 20, 2000, now U.S. Pat. No. 6,537,310

BACKGROUND OF THE INVENTION

The present invention relates generally to implantable metallic medicaldevices. More specifically, the present invention relates to implantablemedical devices, including, for example, surgical and endoluminalvascular grafts, stent grafts, covered stents, skin grafts, shunts, bonegrafts, surgical patches, non-vascular conduits, valvular leaflets,filters, occlusion membranes, sphincters, artificial tendons andligaments. More specifically, the present invention relates toimplantable medical grafts fabricated of metallic or pseudometallicfilms of biocompatible materials and having a plurality of pleats orcorrugations in the film. Where the graft is of a generally tubularshape, the pleats or corrugations are preferably circumferential andaxially positioned along the longitudinal axis of the graft. Inaccordance with a preferred embodiment of the invention, the inventivemedical grafts may have a plurality of microperforations passing throughthe film. The plurality of microperforations may serve multiplepurposes, including, for example, permitting geometric deformation ofthe film, imparting a fabric-like quality to the film, impartingflexibility to the film, permitting tissue ingrowth and promotinghealing. The term “fabric-like” is intended to mean a quality of beingpliable and/or compliant in a manner similar to that found with naturalor synthetic woven fabrics. The inventive medical grafts may have bothperforated and imperforated regions along at least portions of thesurface area of the graft.

The inventive implantable grafts are fabricated entirely ofself-supporting, coherent films made of biocompatible metals orbiocompatible pseudometals. Heretofore in the field of implantablemedical devices, it is unknown to fabricate an implantable medicaldevice that comprises a graft as at least as one of its elements, suchas a stent graft or covered stent, fabricated entirely ofself-supporting, coherent metal or pseudometal materials. As used hereinthe term “graft” is intended to indicate any type of device or part of adevice that comprises essentially a material delimited by two surfaceswhere the distance between said surfaces is the thickness of the graftand exhibits integral dimensional strength to be self-supporting suchthat it is capable of use in vivo without the need for an ancillarysupporting structure, such as a stent or other structural reinforcementto maintain an enlarged in vivo diameter. The inventive graft may havemicroperforations that pass through regions of the thickness of thegraft such that the graft has imperforate regions and microperforateregions, or may have microperforations through all wall surfaces of thegraft or be completely imperforate. The inventive grafts may be formedin planar sheets, toroids, and in other shapes as particularapplications may warrant. However, for purposes of illustration only,the present application will refer to tubular grafts. For purposes ofthis application, the terms “pseudometal” and “pseudometallic” areintended to mean a biocompatible material which exhibits biologicalresponse and material characteristics substantially the same asbiocompatible metals. Examples of pseudometallic materials include, forexample, composite materials and ceramics. Composite materials arecomposed of a matrix material reinforced with any of a variety of fibersmade from ceramics, metals, carbon, or polymers.

When implanted into the body, metals are generally considered to havesuperior biocompatibility than that exhibited by polymers used tofabricate commercially available polymeric grafts. It has been foundthat when prosthetic materials are implanted, integrin receptors on cellsurfaces interact with the prosthetic surface. The integrin receptorsare specific for certain ligands in vivo. If a specific protein isadsorbed on a prosthetic surface and the ligand exposed, cellularbinding to the prosthetic surface may occur by integrin-ligand docking.It has also been observed that proteins bind to metals in a morepermanent fashion than they do to polymers, thereby providing a morestable adhesive surface. The conformation of proteins coupled tosurfaces of most medical metals and alloys appears to expose greaternumbers of ligands and preferentially attract endothelial cells havingsurface integrin clusters to the metal or alloy surface relative toleukocytes. Finally, metals and metal alloys exhibit greater resistanceto degradation of metals relative to polymers, thereby providing greaterlong-term structural integrity and stable interface conditions.

Because of their relatively greater adhesive surface profiles, metalsare also susceptible to short-term platelet activity and/orthrombogenicity. These deleterious properties may be offset byadministration of pharmacologically active antithrombogenic agents inroutine use today. Surface thrombogenicity usually disappears 1-3 weeksafter initial exposure. Antithrombotic coverage is routinely providedduring this period of time for coronary stenting. In non-vascularapplications such as musculoskeletal and dental, metals have alsogreater tissue compatibility than polymers because of similar molecularconsiderations. The best article to demonstrate the fact that allpolymers are inferior to metals is van der Giessen, W J. et al. Markedinflammatory sequelae to implantation of biodegradable andnon-biodegradable polymers in porcine coronary arteries, Circulation,1996: 94(7):1690-7.

Normally, endothelial cells (EC) migrate and proliferate to coverdenuded areas until confluence is achieved. Migration, quantitativelymore important than proliferation, proceeds under normal blood flowroughly at a rate of 25 μm/hr or 2.5 times the diameter of an EC, whichis nominally 10 μm. EC migrate by a rolling motion of the cell membrane,coordinated by a complex system of intracellular filaments attached toclusters of cell membrane integrin receptors, specifically focal contactpoints. The integrins within the focal contact sites are expressedaccording to complex signaling mechanisms and eventually couple tospecific amino acid sequences in substrate adhesion molecules. An EC hasroughly 16-22% of its cell surface represented by integrin clusters.Davies, P. F., Robotewskyi A., Griem M. L. Endothelial cell adhesion inreal time. J. Clin Invest. 1993; 91:2640-2652, Davies, P. F.,Robotewski, A., Griem, M. L., Qualitiative studies of endothelial celladhesion, J. Clin. Invest. 1994; 93:2031-2038. This is a dynamicprocess, which implies more than 50% remodeling in 30 minutes. The focaladhesion contacts vary in size and distribution, but 80% of them measureless than 6 μm², with the majority of them being about 1 μm², and tendto elongate in the direction of flow and concentrate at leading edges ofthe cell. Although the process of recognition and signaling to determinespecific attachment receptor response to attachment sites isincompletely understood, availability of attachment sites will favorablyinfluence attachment and migration. It is known that materials commonlyused as medical grafts, such as polymers, do not become covered with ECand therefore do not heal after they are placed in the arteries. It istherefore an object of this invention to replace polymer grafts withmetal grafts that can potentially become covered with EC and can healcompletely. Furthermore, heterogeneities of materials in contact withblood flow may be controlled by using vacuum deposition techniques toform the materials to make the inventive grafts.

There have been numerous attempts to increase endothelialization ofimplanted medical devices such as stents, including covering the stentwith a polymeric material (U.S. Pat. No. 5,897,911), imparting adiamond-like carbon coating onto the stent (U.S. Pat. No. 5,725,573),covalently binding hydrophobic moieties to a heparin molecule (U.S. Pat.No. 5,955,588), coating a stent with a layer of blue to black zirconiumoxide or zirconium nitride (U.S. Pat. No. 5,649,951), coating a stentwith a layer of turbostatic carbon (U.S. Pat. No. 5,387,247), coatingthe tissue-contacting surface of a stent with a thin layer of a Group VBmetal (U.S. Pat. No. 5,607,463), imparting a porous coating of titaniumor of a titanium alloy, such as Ti—Nb—Zr alloy, onto the surface of astent (U.S. Pat. No. 5,690,670), coating the stent, under ultrasonicconditions, with a synthetic or biological, active or inactive agent,such as heparin, endothelium derived growth factor, vascular growthfactors, silicone, polyurethane, or polytetrafluoroethylene, (U.S. Pat.No. 5,891,507), coating a stent with a silane compound with vinylfunctionality, then forming a graft polymer by polymerization with thevinyl groups of the silane compound (U.S. Pat. No. 5,782,908), graftingmonomers, oligomers or polymers onto the surface of a stent usinginfrared radiation, microwave radiation or high voltage polymerizationto impart the property of the monomer, oligomer or polymer to the stent(U.S. Pat. No. 5,932,299). However, these approaches fail to remedy thelack of clinically acceptable endothelialization of polymer grafts.

It is, therefore, desirable that the inventive graft be fabricatedentirely of metallic and/or pseudometallic materials wherein at least aportion of the wall surfaces of the graft have a plurality of pleats orundulations to provide a self-supporting, stand-alone graft thatexhibits a greater capacity for endothelialization than that ofconventional polymeric grafts.

SUMMARY OF THE INVENTION

In accordance with a preferred embodiment of the invention, there isprovided a self-supporting graft member having a plurality of pleats orcorrugations in wall surfaces thereof and may have a plurality ofmicroperforations passing through the wall thickness of the graft. Whilethe inventive graft member may assume virtually any geometricconfiguration, including sheets, tubes or rings, preferred geometriesfor the graft member are generally planar and generally tubular. Wherepresent, the plurality of microperforations serve to impart geometriccompliance to the graft, geometric distendability to the graft and/orlimit or permit the passage of body fluids or biological matter throughthe graft, such as facilitating transmural endothelialization whilepreventing fluid flow through the wall of the graft under normalphysiological conditions. The plurality of microperforations may alsoimpart a fabric-like quality to the graft by imparting pliability and/orelastic, plastic or superelastic compliance to the graft, such as thatrequired for longitudinal flexibility in the case of a vascular graft.

In a first embodiment, the graft may be made from plastically deformablematerials such that upon application of a force, the microperforationsgeometrically deform to impart permanent enlargement of one or more axesof the graft, such as length in the case of a planar graft, e.g., asurgical patch graft, or diameter, such as in the case of a tubulargraft, e.g., a vascular graft. In a second embodiment, the graft may befabricated of elastic or superelastic materials. Elastic and/orsuperelastic materials will permit the microperforations togeometrically deform under an applied force in a manner that allows fora recoverable change in one or more axes of the graft.

In each of the first and second embodiments of the invention, the graftmay be fabricated in such a manner as to have fabric-like qualities bycontrolling the film thickness, material properties and geometry of theplurality of microperforations. Furthermore, in such cases whereminimally invasive delivery is required, such as for endoluminaldelivery of vascular grafts, the first and second embodiments allow fordelivery using balloon expansion and self-expansion, respectively, or acombination of both. Minimally invasive delivery may also beaccomplished by folding the graft for delivery similar to the manner inwhich an angioplasty balloon is creased and fluted or folded. The graftmay be delivered by unfolding the device in vivo either by assistancesuch as by using a balloon, or by the graft material's plastic, elasticor superelastic properties or by a combination thereof. After delivery,the plurality of microperforations may be patterned in such a manner asto allow for additional dimensional enlargement of the graft member byelastic or plastic deformation such as a radially expansive positivepressure.

The inventive metallic or pseudometallic graft may be employed as asurgically implanted graft, such as, for bypass grafting applicationsthat require access by surgical procedures and suturing the graft to anexisting anatomical structure. The inventive graft is highly suturableand exhibits suture retention strengths comparable to conventionalsynthetic polymeric grafts such as those fabricated from expandedpolytetrafluoroethylene or polyester.

For some applications it is preferable that the size of each of theplurality of microperforations be such as to permit cellular migrationthrough each opening, without permitting fluid flow there through. Inthis manner, for example, blood cannot flow through the plurality ofmicroperforations, in either their deformed or un-deformed state, butvarious cells or proteins may freely pass through the plurality ofmicroperforations to promote graft healing in vivo. For otherapplications, moderate amounts of fluid flow through the plurality ofdeformed or un-deformed microperforations may be acceptable. Forexample, endoluminal saphenous vein grafts may be fabricated withmicroperforations that serve the dual function of permitting transmuralendothelialization while also excluding biological debris, such asthrombus from passing through the wall thickness of the graft,effectively excluding detrimental matter from entering the circulation.In this example, each of the plurality of microperforations in eithertheir deformed or undeformed state, may exceed several hundred microns.

Those skilled in the art will understand that a direct relationshipexists between the size of pores and the overall ratio of expansion ordeformability of an implantable graft. Generally, therefore, it isappreciated that pore sizes must increase in order to increase theeffective attainable degree of expansion or deformation of the graft.

For applications where large deformation and small pore size are bothrequirements, in accordance with another aspect of the inventive graftembodiment, it is contemplated that two or more graft members areemployed such as diametrically concentric grafts for tubularconfigurations. The two or more graft members have a pattern of aplurality of microperforations passing there through, with the pluralityof patterned microperforations being positioned out of phase relative toone another such as to create a tortuous cellular migration pathwaythrough the wall of the concentrically engaged first and second graftmembers as well as a smaller effective pore size. In order to facilitatecellular migration through and healing of the first and second graftmembers in vivo, it may be preferable to provide additional cellularmigration pathways that communicate between the plurality ofmicroperforations in the first and second graft members. Theseadditional cellular migration pathways, if necessary, may be impartedas 1) a plurality of projections formed on either the luminal surface ofthe second graft or the abluminal surface of the first graft, or both,which serve as spacers and act to maintain an annular opening betweenthe first and second graft members that permits cellular migration andcellular communication between the plurality of microperforations in thefirst and second graft members, 2) a plurality of microgrooves, whichmay be random, radial, helical, or longitudinal relative to thelongitudinal axis of the first and second graft members, the pluralityof microgrooves being of a sufficient size to permit cellular migrationand propagation along the groove, the microgrooves serve as cellularmigration conduits between the plurality of microperforations in thefirst and second graft members, or 3) where the microperforations aredesigned to impart an out of plane motion of the graft material upondeformation, thereby keeping a well defined space between the planesoriginally defining the facing surfaces of the grafts.

The graft member or members may be formed as a monolayer film, or may beformed from a plurality of film layers formed one upon another. Theparticular material used to form each layer of biocompatible metaland/or pseudometal is chosen for its biocompatibility, corrosion-fatigueresistance and mechanical properties, i.e., tensile strength, yieldstrength. The metals include, without limitation, the following:titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium,silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt,palladium, manganese, molybdenum and alloys thereof, such aszirconium-titanium-tantalum alloys, nitinol, and stainless steel.Additionally, each layer of material used to form the graft may be dopedwith another material for purposes of improving properties of thematerial, such as radiopacity or radioactivity, by doping with tantalum,gold, or radioactive isotopes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of the inventive graft.

FIG. 2A is a fragmentary plan view depicting a first pattern ofmicroperforations useful in the present invention.

FIG. 2B is a fragmentary plan view depicting a second pattern ofmicroperforations useful in the present invention.

FIG. 2C is a fragmentary plan view depicting a third pattern ofmicroperforations useful in the present invention.

FIG. 2D is a fragmentary plan view depicting a fourth pattern ofmicroperforations useful in the present invention.

FIG. 3A is photomicrograph depicting the inventive graft having thefirst pattern of microperforation depicted in FIG. 2A in a geometricallyundeformed state.

FIG. 3B is a photomicrograph of the inventive graft illustrated in FIG.3A showing the microperforations in a geometrically deformed state.

FIG. 4 is a diagrammatic illustration depicting geometric deformation ofthe fourth pattern of microperforations in FIG. 2D.

FIG. 5 is a diagrammatic cross-sectional view illustration depicting theinventive graft assuming a folded condition suitable for endoluminaldelivery.

FIG. 6 is a photographic illustration of the inventive graft used as astent covering.

FIG. 7 is a photographic illustration of the inventive graft deformedapproximately 180 degrees along its longitudinal axis illustrating thefabric-like quality of the graft.

FIG. 8A is a photographic illustration of the inventive graftcircumferentially covering a braided expansion member and mounted on anexpansion jig that exerts a compressive force along the longitudinalaxis of the braided expansion member and which radially expands thebraided expansion member.

FIG. 8B is a photographic illustration of the inventive graft radiallyexhibiting radial compliance under the influence of a radially expansiveforce.

FIG. 9 is a flow diagram depicting alternate embodiments of making theinventive graft.

FIG. 10A is a histology slide, stained with hematoxylin and eosin, froma 28 day explanted swine carotid artery having the inventive graftimplanted therein.

FIG. 10B is a histology slide, stained with hematoxylin and eosin, froma 28 day explanted swine carotid artery having the inventive graftimplanted therein.

FIG. 11 is a perspective view of an alternative embodiment of theinventive graft.

FIG. 12 is a cross-sectional view taken along line 12-12 of FIG. 11.

FIG. 13 is an magnified view of region 13 of FIG. 12.

FIG. 14 is a perspective view of a forming mandrel for making thealternative embodiment of the inventive graft.

FIG. 15 is a cross-sectional view taken along line 15-15 of FIG. 14.

FIG. 16 is a perspective view of a second alternative embodiment of theinventive graft.

FIG. 17 is a perspective view taken along line 17-17 of FIG. 16.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

With the foregoing as background, we turn now to a description of thepresent invention with reference the preferred embodiments thereof andwith reference to the accompanying figures. As noted above, theinventive microporous metallic implantable devices may assume a widenumber of geometric configurations, including, for example, planarsheets, tubes or toroids. For ease of reference, however, theaccompanying figures and the following description of the invention willrefer to tubular implantable graft members. Those skilled in the art,however, will understand that this is merely an exemplary geometricconfiguration and is not intended to limit the scope of the invention totubular members or be limited in application to graft members.

The inventive metal devices are preferably fabricated by thin filmvacuum deposition techniques such as sputtering or physical vapordeposition processes. In accordance with the present invention, it ispreferable to fabricate the inventive implantable devices by vacuumdeposition. Vacuum deposition permits greater control over many materialcharacteristics and properties of the resulting formed device. Forexample, vacuum deposition permits control over grain size, grain phase,grain material composition, bulk material composition, surfacetopography, mechanical properties, such as transition temperatures inthe case of a shape memory alloy. Moreover, vacuum deposition processespermit creation of devices with greater material purity without theintroduction of large quantities of contaminants that adversely affectthe material, mechanical or biological properties of the implanteddevice. Vacuum deposition techniques also lend themselves to fabricationof more complex devices than those susceptible of manufacture byconventional cold-working techniques. For example, multi-layerstructures, complex geometrical configurations, extremely fine controlover material tolerances, such as thickness or surface uniformity, areall advantages of vacuum deposition processing.

In vacuum deposition technologies, materials are formed directly in thedesired geometry, e.g., planar, tubular, etc. and have a pre-determinedsurface topography based upon the surface topography of a depositionsubstrate onto which a metal or pseudometal is deposited, conforming tothe substrate topography. The common principle of vacuum depositionprocesses is to take a material in a minimally processed form, such aspellets or thick foils, known as the source material and atomize them.Atomization may be carried out using heat, as is the case in physicalvapor deposition, or using the effect of collisional processes, as inthe case of sputter deposition, for example. In some forms ofdeposition, a process, such as laser ablation, which createsmicroparticles that typically consist of one or more atoms, may replaceatomization; the number of atoms per particle may be in the thousands ormore. The atoms or particles of the source material are then depositedon a substrate or mandrel to directly form the desired object. In otherdeposition methodologies, chemical reactions between ambient gasintroduced into the vacuum chamber, i.e., the gas source, and thedeposited atoms and/or particles are part of the deposition process. Thedeposited material includes compound species that are formed due to thereaction of the solid source and the gas source, such as in the case ofchemical vapor deposition. In most cases, the deposited material is theneither partially or completely removed from the substrate, to form thedesired product.

A first advantage of vacuum deposition processing is that vacuumdeposition of the metallic and/or pseudometallic films permits tightprocess control and films may be deposited that have regular,homogeneous atomic and molecular pattern of distribution along theirfluid-contacting surfaces. This avoids the marked variations in surfacecomposition, creating predictable oxidation and organic adsorptionpatterns and has predictable interactions with water, electrolytes,proteins and cells. Particularly, EC migration is supported by ahomogeneous distribution of binding domains that serve as natural orimplanted cell attachment sites, in order to promote unimpeded migrationand attachment.

Secondly, in addition to materials and devices that are made of a singlemetal or metal alloy, henceforth termed a layer, the inventive graftsmay be comprised of a layer of biocompatible material or of a pluralityof layers of biocompatible materials formed upon one another into aself-supporting multilayer structure. Multilayer structures aregenerally known to increase the mechanical strength of sheet materials,or to provide special qualities by including layers that have specialproperties such as superelasticity, shape memory, radio-opacity,corrosion resistance etc. A special advantage of vacuum depositiontechnologies is that it is possible to deposit layered materials andthus films possessing exceptional qualities may be produced (cf., H.Holleck, V. Schier: Multilayer PVD coatings for wear protection, Surfaceand Coatings Technology, Vol. 76-77 (1995) pp. 328-336). Layeredmaterials, such as superstructures or multilayers, are commonlydeposited to take advantage of some chemical, electronic, or opticalproperty of the material as a coating; a common example is anantireflective coating on an optical lens. Multilayers are also used inthe field of thin film fabrication to increase the mechanical propertiesof the thin film, specifically hardness and toughness.

Thirdly, the design possibilities for possible configurations andapplications of the inventive graft are greatly enhanced by employingvacuum deposition technologies. Specifically, vacuum deposition is anadditive technique that lends itself toward fabrication of substantiallyuniformly thin materials with potentially complex three dimensionalgeometries and structures that cannot be cost-effectively achieved, orin some cases achieved at all, by employing conventional wroughtfabrication techniques. Conventional wrought metal fabricationtechniques may entail smelting, hot working, cold working, heattreatment, high temperature annealing, precipitation annealing,grinding, ablation, wet etching, dry etching, cutting and welding. Allof these processing steps have disadvantages including contamination,material property degradation, ultimate achievable configurations,dimensions and tolerances, biocompatibility and cost. For exampleconventional wrought processes are not suitable for fabricating tubeshaving diameters greater than about 20 mm diameter, nor are suchprocesses suitable for fabricating materials having wall thicknessesdown to about 5 μm with sub-μm tolerances.

While the inventive self-supporting metal or pseudometal graft may befabricated of conventionally fabricated wrought materials, in accordancewith the best mode contemplated for the present invention, the inventivegraft is preferably fabricated by vacuum deposition techniques. Byvacuum depositing the metal and/or pseudometallic film as the precursormaterial for the inventive graft, it is possible to more stringentlycontrol the material, biocompatibility and mechanical properties of theresulting film material and graft than is possible with conventionallyfabricated graft-forming materials. The inventive self-supporting graftmay be used alone, i.e., the whole implantable device may be made of asingle graft, or it may be a part of a structure where the graft is usedin conjunction either with other grafts, or in conjunction with otherstructural elements, such as scaffolds, stents, and other devices. Theterm “in conjunction” may mean actual connection, such as that made bywelding, fusing, or other joining methods, as well as being made fromthe same piece of material by forming some area of the piece into agraft and some other area of the piece into another member or part ofthe device.

With particular reference to FIG. 1, the inventive implantable medicaldevice is illustrated as a graft 10. Graft 10 consists generally of abody member 12 having a first surface 14 and a second surface 16 and athickness 18 intermediate the first surface 14 and the second surface16. A plurality of microperforations 20 is provided and pass through thethickness 18 of the body member 12 with interperforation regions 22 ofthe body member 12 between adjacent microperforation 20. The pluralityof microperforations 20 each preferably have a geometric configurationthat is susceptible of geometric change, such that the open surface areaof each microperforation 20 may change under an externally applied load.Each of the plurality of microperforations 20 in the undeformed statepreferably has an open surface area less than about 2 mm², with thetotal open surface area of the graft in the undeformed state beingbetween 0.001 to 99%. The open surface area of the plurality ofmicroperforations and the open surface area of the graft may changeconsiderably upon deformation of the plurality of microperforations 20.Both the size of the microperforations 20 in the deformed and undeformedstate and the total open area of the graft 10 in the deformed andundeformed state may be selected in view of the following non-exclusivefactors based on the graft application: 1) the desired compliance of thegraft 10, 2) the desired strength of the graft 10, 3) desired stiffnessof the graft 10, 4) the desired degree of geometric enlargement of themicroperforations 20 upon deformation and 5) in some cases, such as withvascular grafts, the desired delivery profile and post delivery profile.

In accordance with a preferred embodiment of the present invention, theplurality of microperforations 20 is patterned in such a manner as todefine deformation regions of the body member 12. The thickness 18 isbetween 0.1 μm and 75 μm, preferably between 1 μm and 50 μm., and mostpreferably between about 2 μm and 25 μm. When fabricated within thesethickness ranges, the graft 10 has a thickness 18 which is thinner thanthe wall thickness of conventional non-metallic implantable grafts andthat of conventional metal endoluminal stents.

The plurality of microperforations is patterned in a regular arrayforming a regular array of microperforations 20 in both the longitudinaland circumferential axes of the body member 12. For purposes ofreference, the pattern of microperforations 20 will, hereinafter, bedescribed with reference to a planar X-Y axes, which in a tubular memberwill correspond to the longitudinal or circumferential axes of thetubular member. Those of ordinary skill in the art will understand thatreference to X-axis or Y-axis when applied to a tubular member may beused such that the term “X-axis” may correspond to either thelongitudinal axis or circumferential direction of the tubular member andthe term “Y-axis” may refer to the corresponding circumferentialdirection or longitudinal axis or the tubular member.

It will be appreciated by those of ordinary skill in the art thatindividual different geometric patterns may have associated intendeduses, function or mechanical requirements of a particular device. Thus,the particular intended use of the implantable member 10 will be aconsideration in the selection of the particular geometric pattern forthe plurality of microperforations 20. For example, where theimplantable member 10 has an intended use as a free-standing implantableendoluminal vascular graft, a large circumferential expansion ratio andlongitudinal flexibility may be desirable. Thus, a particular geometryof the plurality of microperforations 20 that offers these propertieswill be selected. The plurality of microperforations 20 also affect thematerial properties of the implantable member 10. For example, thegeometry each microperforation 20 may be altered so that eachmicroperforation 20 exhibits stress-strain relief capabilities or themicroperforations 20 may control whether geometric deformation of themicroperforations 20 are plastic, elastic or superelastic deformation.Thus, both the geometry of the individual microperforations 20, theorientation of the microperforations 20 relative to the X-Y axis of theimplantable member 10 and the pattern of the microperforations 20 may beselected to directly impart, affect or control the mechanical andmaterial properties of the implantable member 10.

Different geometric patterns for the plurality of microperforations 20in accordance with the preferred embodiments of the invention areillustrated in FIGS. 2A-2C. FIG. 2A illustrates a first geometry foreach of the plurality of microperforations 20. In accordance with thisfirst geometry, each of the plurality of microperforations 20 consist ofgenerally elongated slots 32 a, 32 b. Each of the generally elongatedslots 32 a, 32 b preferably include terminal fillets 34 on opposing endsof each elongated slot 32 a, 32 b. The terminal fillets 34 serve astrain relief function that aids in strain distribution through theinterperforation regions 22 between adjacent slots 32. FIG. 2A furtherillustrates a first geometric pattern for the plurality ofmicroperforations 32 a, 32 b, wherein a first row of a plurality ofmicroperforations 32 a is provided with adjacent microperforations 32 abeing arrayed in end-to-end fashion along a common axis, and a secondrow of a plurality of microperforations 32 b is provided with adjacentmicroperforations 32 b being arrayed in end-to-end fashion along acommon axis with one another and with the microperforations 32 a. Thefirst row of microperforations 32 a and the second row ofmicroperforations 32 b are offset or staggered from one another, with anend of a microperforation 32 a being laterally adjacent to anintermediate section of a microperforation 32 b, and an end ofmicroperforation 32 b being laterally adjacent an intermediate sectionof a microperforation 32 a.

The first geometry 30 of the plurality of microperforations 32 a, 32 billustrated in FIG. 2A permits a large deformation along an axisperpendicular to a longitudinal axis of the slots. Thus, where thelongitudinal axis of slots 32 a, 32 b is co-axial with the longitudinalaxis of the implantable member 10, deformation of the slots 32 a, 32 bwill permit circumferential compliance and/or expansion of theimplantable member 10. Alternatively, where the longitudinal axis of theslots 32 a, 32 b is parallel to the circumferential axis of theimplantable member 10, the slots 32 a, 32 b permit longitudinalcompliance, flexibility and expansion of the implantable member 10.

FIG. 2B illustrates a second geometry 40 for the plurality ofmicroperforations 20 and consists of a plurality of microperforations 42a, 44 b, again having a generally elongate slot-like configuration likethose of the first geometry 30. In accordance with this second geometry40, individual microperforations 42 a and 44 b are oriented orthogonalrelative to one another. Specifically, a first microperforation 42 a isoriented parallel to an X-axis of the implantable member 10, while afirst microperforation 44 b is positioned adjacent to the firstmicroperforation 44 a along the X-axis, but the first microperforation44 b is oriented perpendicular to the X-axis of the implantable member10 and parallel to the Y-axis of the implantable member 10. Like thefirst geometry, each of the plurality of microperforations 42 a, 44 bmay include a terminal fillet 44 at opposing ends of the slot of eachmicroperforation in order to serve a strain relief function and transmitstrain to the interperforation region 22 between adjacentmicroperforations. This second geometry 40 offers a balance in bothcompliance and degree of expansion in both the X and Y-axes of theimplantable device 12

In each of FIGS. 2A and 2B, each of the microperforations 32 a, 32 b, 42a, 44 b has a generally longitudinal slot configuration. Each of thegenerally longitudinal slots may be configured as a generally linear orcurvilinear slot. In accordance with the preferred embodiments of theinvention, however, it is preferred to employ generally linear slots.

FIG. 2C illustrates a third preferred geometry 50 for the plurality ofmicroperforations. In accordance with this third geometry 50, each ofthe plurality of microperforations 52 has a generally trapezoidal ordiamond-like shape with interperforation graft regions 56 betweenadjacent pairs of microperforations 52. It will be appreciated that thethird geometry 50 may be achieved by geometrically deforming the firstgeometry 30 along an axis perpendicular to the longitudinal axis of theplurality of microperforations 32 a, 32 b. Similarly, the first geometry30 may be achieved by deforming microperforations 52 in the thirdgeometry 50 along either an X-axis or a Y-axis of the implantable member10.

FIGS. 3A and 3B are photomicrographs illustrating the inventiveimplantable device 12 having a plurality of microperforations formed asgenerally longitudinal slots 32 a, 32 b in accordance with the firstgeometry depicted in FIG. 2A. Each of the plurality of microperforationswere formed with an orientation parallel to the longitudinal axis of theimplantable device 12. The implantable device 12 consists of a 6 mminner diameter NiTi shape memory tubular graft member having a wallthickness of 5 μm. FIG. 3A depicts the plurality of microperforations 32a and 32 b in their undeformed state, while FIG. 3B depicts theplurality of microperforations 32 a and 32 b in their geometricallydeformed state under the influence of stain applied perpendicular to thelongitudinal axis of the implantable graft 12. It may be clearlyunderstood that geometric deformation of the plurality ofmicroperforations 32 a, 32 b permitted circumferential expansion of theinventive graft. The dimensions of each of the plurality ofmicroperforations in their undeformed state depicted in FIGS. 3A and 3Bwas 430 μm in length, 50 μm width, with the terminal fillets having a 50μm diameter.

In accordance with a fourth geometry of the plurality ofmicroperforations 20 illustrated in FIGS. 2D and 4, each of theplurality of microperforations 20 have a generally tri-legged orY-shaped configuration. The Y-shaped configuration of each of theplurality of microperforations 20 has three co-planar radiallyprojecting legs 31 a, 31 b, 31 c, each offset from the other by an angleof about 120 degrees thereby forming a generally Y-shape. Each of thethree co-planar radially projecting legs 31 a, 31 b, 31 c may besymmetrical or asymmetrical relative to one another. However, in orderto achieve uniform geometric deformation across the entire graft bodymember 12, it is preferable that each of the plurality ofmicroperforations 20 has geometric symmetry. Those skilled in the artwill recognize that beyond the two particular patterns described hereany number of different patterns may be used without significantlydeparting from the inventive graft concept described in the presentpatent.

Those skilled in the art will understand that each of themicroperforations 20 are capable of undergoing deformation uponapplication of a sufficient force. In a tubular geometry, the graft 12may deform both circumferentially and longitudinally. As is illustratedin FIG. 3 a, each of the plurality of elongated slots may deform intoopened microperforations which assume a generally rhomboidal shape.Similarly, Y-shaped microperforations 20 shown in FIG. 4 are capable ofdeformation into generally circular or oval open microperforations 21.The deformation regions 22 between adjacent microperforations 20facilitate deformation of each of the plurality of microperforations 20by deforming to accommodate opening of each of the plurality ofmicroperforations 20.

As depicted in FIG. 5, the inventive graft 12 may be folded to assume asmaller diametric profile for endoluminal delivery. In order tofacilitate folding, the pattern of the plurality of microperforations 20may be fashioned to create a plurality of folding regions 23, thatconstitute relatively weakened regions of the graft 12, to permitfolding the graft 12 along folding regions 23.

FIG. 6 is a photographic illustration of the inventive microporous graft12 circumferentially mounted onto an endoluminal stent 5. It may bereadily seen that the microporous graft 12 exhibits mechanicalproperties of high longitudinal flexibility and both radial andcircumferential compliance.

FIG. 7 is a photographic illustration of the inventive microporous graft12 mounted onto mandrel and flexed approximately 180 degrees along itslongitudinal axis. Upon longitudinal flexion, the inventive graft 12undergoes a high degree of folding with a plurality of circumferentiallyoriented folds 7, characteristic of its fabric-like qualities.

FIGS. 8A and 8B are photographic reproductions illustrating the highdegree of circumferential compliance of the inventive microporous graft12. A 6 mm microporous graft having a 5 μm wall thickness was mountedconcentrically over a braided pseudostent. An axial force was appliedalong the longitudinal axis of the braided pseudostent causing thepseudostent to radially expand and exert a circumferentially expansiveforce to the inventive graft 12. As is clearly depicted in FIGS. 8A and8B the plurality of micropores in the inventive graft 12 geometricallydeform thereby permitting circumferential expansion of the graft 12.

Thus, one embodiment of the present invention provides a new metallicand/or pseudometallic implantable graft that is biocompatible,geometrically changeable either by folding and unfolding or byapplication of a plastically, elastically or superelastically deformingforce, and capable of endoluminal delivery with a suitably smalldelivery profile. Suitable metal materials to fabricate the inventivegraft are chosen for their biocompatibility, mechanical properties,i.e., tensile strength, yield strength, and their ease of fabrication.The compliant nature of the inventive graft material may be employed toform the graft into complex shapes by deforming the inventive graft overa mandrel or fixture of the appropriate design. Plastic deformation andshape setting heat treatments may be employed to ensure the inventiveimplantable members 10 retain a desired conformation.

According to a first preferred method of making the graft of the presentinvention, the graft is fabricated of vacuum deposited metallic and/orpseudometallic films. With particular reference to FIG. 9, thefabrication method 100 of the present invention is illustrated. Aprecursor blank of a conventionally fabricated biocompatible metal orpseudometallic material may be employed at step 102. Alternatively, aprecursor blank of a vacuum deposited metal or pseudometallic film maybe employed at step 104. The precursor blank material obtained eitherfrom step 102 or step 104 is then preferably masked at step 108 leavingexposed only those regions defining the plurality of microperforations.The exposed regions from step 108 are then subjected to removal eitherby etching at step 110, such as by wet or dry chemical etchingprocessing, with the etchant being selected based upon the material ofthe precursor blank, or by machining at step 112, such as by laserablation or EDM. Alternatively, when employing the vacuum depositionstep 104, a pattern mask corresponding to the plurality ofmicroperforations may be interposed at step 106 between the target andthe source and the metal or pseudometal deposited through the patternmask to form the patterned microperforations. Further, when employingthe vacuum deposition step 104, plural film layers maybe deposited toform a multilayer film structure of the film prior to or concurrentlywith forming the plurality of microperforations.

Thus, the present invention provides a new metallic and/orpseudometallic implantable graft that is biocompatible, compliant,geometrically changeable either by folding and unfolding or byapplication of a plastically, elastically or superelastically deformingforce, and, in some cases, capable of endoluminal delivery with asuitably small delivery profile and suitably low post-delivery profile.Suitable metal materials to fabricate the inventive graft are chosen fortheir biocompatibility, mechanical properties, i.e., tensile strength,yield strength, and in the case where vapor deposition is deployed,their ease of deposition include, without limitation, the following:titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium,silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt,palladium, manganese, molybdenum and alloys thereof, such aszirconium-titanium-tantalum alloys, nitinol, and stainless steel.Examples of pseudometallic materials potentially useful with the presentinvention include, for example, composite materials and ceramics.

The present invention also provides a method of making the inventiveexpandable metallic graft by vacuum deposition of a graft-forming metalor pseudometal and formation of the microperforations either by removingsections of deposited material, such as by etching, EDM, ablation, orother similar methods, or by interposing a pattern mask, correspondingto the microperforations, between the target and the source duringdeposition processing. Alternatively, a pre-existing metal and/orpseudometallic film manufactured by conventional non-vacuum depositionmethodologies, such as wrought hypotube or sheet, may be obtained, andthe microperforations formed in the pre-existing metal and/orpseudometallic film by removing sections of the film, such as byetching, EDM, ablation, or other similar methods. An advantage ofemploying multilayer film structures to form the inventive graft is thatdifferential functionalities may be imparted in the discrete layers. Forexample, a radiopaque material such as tantalum may form one layer of astructure while other layers are chosen to provide the graft with itsdesired mechanical and structural properties.

In accordance with the preferred embodiment of fabricating the inventivemicroporous metallic implantable device in which the device isfabricated from vacuum deposited nitinol tube, a cylindricaldeoxygenated copper substrate is provided. The substrate is mechanicallyand/or electropolished to provide a substantially uniform surfacetopography for accommodating metal deposition thereupon. A cylindricalhollow cathode magnetron sputtering deposition device was employed, inwhich the cathode was on the outside and the substrate was positionedalong the longitudinal axis of the cathode. A cylindrical targetconsisting either of a nickel-titanium alloy having an atomic ratio ofnickel to titanium of about 50-50% and which can be adjusted by spotwelding nickel or titanium wires to the target, or a nickel cylinderhaving a plurality of titanium strips spot welded to the inner surfaceof the nickel cylinder, or a titanium cylinder having a plurality ofnickel strips spot welded to the inner surface of the titanium cylinderis provided. It is known in the sputter deposition arts to cool a targetwithin the deposition chamber by maintaining a thermal contact betweenthe target and a cooling jacket within the cathode. In accordance withthe present invention, it has been found useful to reduce the thermalcooling by thermally insulating the target from the cooling jacketwithin the cathode while still providing electrical contact to it. Byinsulating the target from the cooling jacket, the target is allowed tobecome hot within the reaction chamber. Two methods of thermallyisolating the cylindrical target from the cooling jacket of the cathodewere employed. First, a plurality of wires having a diameter of 0.0381mm were spot welded around the outer circumference of the target toprovide an equivalent spacing between the target and the cathode coolingjacket. Second, a tubular ceramic insulating sleeve was interposedbetween the outer circumference of the target and the cathode coolingjacket. Further, because the Ni—Ti sputtering yields can be dependant ontarget temperature, methods which allow the target to become uniformlyhot are preferred.

The deposition chamber was evacuated to a pressure less than or about2-5×10⁻⁷ Torr and pre-cleaning of the substrate is conducted undervacuum. During the deposition, substrate temperature is preferablymaintained within the range of 300 and 700 degrees Centigrade. It ispreferable to apply a negative bias voltage between 0 and −1000 volts tothe substrate, and preferably between −50 and −150 volts, which issufficient to cause energetic species arriving at the surface of thesubstrate. During deposition, the gas pressure is maintained between 0.1and 40 mTorr but preferably between 1 and 20 mTorr. Sputteringpreferably occurs in the presence of an Argon atmosphere. The argon gasmust be of high purity and special pumps may be employed to reduceoxygen partial pressure. Deposition times will vary depending upon thedesired thickness of the deposited tubular film. After deposition, theplurality of microperforations are formed in the tube by removingregions of the deposited film by etching, such as chemical etching,ablation, such as by excimer laser or by electric discharge machining(EDM), or the like. After the plurality of microperforations are formed,the formed microporous film is removed from the copper substrate byexposing the substrate and film to a nitric acid bath for a period oftime sufficient to remove dissolve the copper substrate.

Example

A 5 μm thick NiTi graft having a pattern of microperforations consistingof parallel staggered longitudinally oriented linear slots, each slotbeing 430 μm length, 25 μm width, and having 50 μm diameter fillets oneach end of each linear slot, was mounted onto a 6 mm NiTi stent anddelivered endoluminally to the left carotid artery of a swine. After 28days, the swine was euthanized, and the graft explanted from the leftcarotid artery. Samples were prepared using standard hematoxylin andeosin staining procedures, and microscope slides prepared. Asillustrated in FIG. 10A histology of the explanted samples revealedcomplete endothelialization around the graft 12, negligible neointimalproliferation with the absence of trauma to the internal elastic lamina.FIG. 10B is a sample indicating cross-talk between the arterialsuperficial and deep layers with the transmural formation of smallcapillaries.

Alternate embodiments of the inventive graft are depicted in FIGS. 11-13and FIGS. 16-17, and a forming substrate for making the alternateembodiments is depicted in FIGS. 14-15. With particular reference toFIGS. 11-13, a graft 60 having a generally tubular configuration with acentral longitudinal lumen 61 is depicted. Graft 60 consists generallyof a graft body member 62 that is preferably formed entirely of at leastone vacuum deposited metallic or pseudometallic material as describedabove with reference to the previously described inventive graftmaterials. The graft body member 62 has first and second wall surfacesforming lumenal and ablumenal surfaces of the graft body member and aplurality of corrugations or pleats 64 forming an undulating pattern ofpeaks 65 and valleys 67 in wall surfaces of the graft body member 62.

As illustrated in FIG. 13, the graft 60 preferably has a plurality ofmicroperforations 266 passing through the wall surfaces of the graftbody member 62 and communicating between the ablumenal and lumenal wallsurfaces of the graft 60. Like the previously described embodiments ofthe inventive graft, the plurality of microperforations 266 in theinventive graft 60 may be formed of a wide variety of geometries anddimensions so as impart geometric compliance to the graft, geometricdistendability to the graft and/or limit or permit the passage of bodyfluids or biological matter through the graft, such as facilitatingtransmural endothelialization while preventing fluid flow through thewall of the graft under normal physiological conditions. The pluralityof microperforations may also impart a fabric-like quality to the graftby imparting pliability and/or elastic, plastic or superelasticcompliance to the graft, such as that required for longitudinalflexibility in the case of a vascular graft.

The plurality of microperforations 266 may be present along the entirelongitudinal length of the graft body member 62 and about the entirecircumferential axis of the graft member 62. Alternatively, theplurality of microperforations 266 may be present only in selectedregions along either the longitudinal length or the circumferential axisof the graft body member 62. The positioning of the plurality ofmicroperforations 266 may be selected based upon various criteria,including, without limitation, the indication of use of the graft, theanatomical placement of the graft, and whether the graft is surgicallyimplanted and requires sutures or whether it is used endoluminallywithout sutures.

Turning to FIGS. 16-17 there is depicted a second alternative embodimentof the inventive graft 70. Like graft 60 depicted in FIGS. 11-13, graft70 consists of a generally tubular graft body member 72 having first andsecond wall surfaces forming lumenal and ablumenal surfaces of thetubular graft body member 72, and a plurality of circumferentialcorrugations or pleats 74 forming an undulating pattern of peaks 75 andvalleys 77 in the wall surfaces of the tubular graft body member 72. Theplurality of corrugations or pleats 74 are preferably positioned alongan intermediate region 76 of the graft 70, with opposing end regions 71,73, that form proximal and distal ends of the graft 70, having nocorrugations or pleats 74. Alternatively, the proximal and distal endsof the graft 70 may have longitudinal regions with circumferentialcorrugations or pleats 74 and other longitudinal regions withoutcircumferential corrugations or pleats 74, thereby having staggeredarrays of corrugated and non-corrugated regions at the opposing ends 71,73 of the graft 70.

In one aspect of the inventive graft 70 the opposing end regions 71, 73of the graft body member 72 may have a z-axis thickness that is eithergreater than or less than the z-axis thickness of the intermediateregion 76. Additionally, a plurality of suture apertures 78 are providedand preferably pass through the opposing ends 71, 73 of the graft 70 andpermit sutures 79 to pass through the suture apertures 78 for purposesof affixing the graft 70 to anatomical structures in vivo. In oneembodiment of the invention, the suture apertures/openings may have agenerally cruciform-shaped slot pattern 78 a or a generally Y-shapedslot pattern 78 b.

Like each of the foregoing embodiments, the grafts 60 and 70 arepreferably fabricated entirely of biocompatible metal and/orpseudometallic materials. By fashioning the inventive grafts 60, 70entirely of biocompatible metal and/or pseudometallic materials, thegrafts 60, 70 exhibit a greater capacity for endothelialization withoutthe need for pre-clotting as is the case with polyethylene or DACRONgrafts, and provide highly hospitable surface for re-endothelializationsimilar to many metal stents.

It will be understood by those skilled in the art that providing thecircumferential corrugations or pleats 64, 74 in grafts 60, 70 imparts alarge degree of longitudinal flexibility to the grafts 60, 70 andpermits the grafts to bend in excess of 180 degrees about itslongitudinal axis. This large degree of longitudinal flexibility in anall metal or pseudometallic graft permits the graft to traverse highlytortuous delivery pathways when used as either an endoluminal graft oras a surgically-implanted graft, and be highly compliant and flexibleafter implantation to accommodate normal flexion and extension duringambulatory motion of the patient.

As noted above, the preferred method for fabricating the inventivegrafts 60, 70 is by physical vapor deposition of a metal orpseudometallic material onto a sacrificial substrate or mandrel. Asuitable sacrificial substrate or mandrel for fabricating the inventivegrafts 60, 70 is illustrated in FIGS. 14-15. A generally cylindricalsubstrate 69 is provided for vacuum deposition. The generallycylindrical substrate may be either a solid or a tubular blank of ametal material 66 that is susceptible to differential degradationrelative to the metal graft deposited thereupon during vacuumdeposition. In order to form the inventive grafts 60, 70, the generallycylindrical substrate 69 is formed with a plurality of circumferentialundulations defining a plurality of peaks 66 and valleys 68. Theplurality of peaks 66 and valleys 68 in the cylindrical substrate 69 arepositioned to correspond to the position of the peaks and valleys formedin the conformal deposited layer that forms the grafts 60, 70. Theremaining process parameters describe above may be followed to form theplurality of micro perforations in the grafts 60, 70.

While the present invention has been described with reference to itspreferred embodiments, those of ordinary skill in the art willunderstand and appreciate that variations in materials, dimensions,geometries, and fabrication methods may be or become known in the art,yet still remain within the scope of the present invention which islimited only by the claims appended hereto.

What is claimed is:
 1. A method of making an implantable medical graftcomprising the steps of: a. Providing a generally tubular implantablemedical graft having a continuous cross section, the generally tubularimplantable medical graft comprising a graft-forming material selectedfrom the group consisting of biocompatible metals and pseudometals, thegraft forming material including circumferential corrugations defined bya radially undulating pattern of longitudinally alternating radiallyextending peaks and valleys in an abluminal wall surface of thegraft-forming material and a radially undulating longitudinallyalternating pattern of radially extending peaks and valleys in a luminalwall surface of the graft-forming material, wherein each peak in theluminal surface is longitudinally coincident with each peak in theabluminal surface and each valley in the luminal surface islongitudinally coincident with each valley in the abluminal surface,wherein the peaks and valleys are disposed along at least a portion ofthe longitudinal axis of the graft-forming material and at least one ofa plurality of non-undulated circumferential regions is positioned atthe end regions of the graft-forming material; and b. forming aplurality of microperforations disposed through the corrugations definedby coincident peaks and the coincident valleys wherein the plurality ofmicroperforations in combination with the corrugations providerecoverable compliance to the graft.
 2. The method of claim 1, whereinforming the plurality of microperforations comprises: a. Masking regionsthat are to remain; and b. Removing material from the unmasked regions.3. The method of claim 2, wherein removing material comprises etching.4. The method of claim 3, wherein the etching method is selected fromthe group comprising wet chemical etching processing or dry chemicaletching processing.
 5. The method of claim 2, wherein removing materialcomprises machining.
 6. The method of claim 5, wherein the machiningmethod is selected from the group comprising laser ablation, electricaldischarge machining, electrochemical machining, cutting, or grinding. 7.The method according to claim 1, further comprising the step of formingat least one of a plurality of openings with suture retention strengththrough the wall thickness of at least one non-undulating region of thegraft-forming material.